The impact of tumor microenvironments on stem cells

Stem cells are defined as cells that possess the ability to both self-renew and differentiate into specialized, mature cell types, and the choice between maintenance and differentiation in stem cells is tightly controlled by both intrinsic and extrinsic mechanisms. The extrinsic regulation of stem cells in vivo is largely under the control of the local multi-cellular microenvionment, also known as the “stem cell niche.” Furthermore, in tumor-bearing hosts, stem cells might also be affected within their niches by the tumor microenvironment (TME). Although cancer stem cells (CSCs) and tumor-initiating cells have been extensively studied in the context of the TME over the previous decade, the impact of the TME on normal tissue stem and progenitor cells has not been as well investigated. As normal tissue stem or progenitor cells are ultimately responsible for tissue regeneration following targeted anti-cancer therapies in most tissue types, understanding how normal tissue stem or progenitor cells are influenced by TMEs is of great importance. Therefore, this review is focused on the effects of TMEs on normal tissue stem cells.